The objective of our proposal is to define the contribution of circulating, as well as locally generated angiotensins, prostaglandins, and kinins to the regulation of adrenergic nervous activity and vascular tone. We will study neurohormonal interactions in several organs (heart, spleen, kidney, mesenteric and pancreatic vasculature) of rat and rabbit. 1) Interactions of angiotensins and adrenergic nervous system. We will examine the effect of synthetic tetradecapeptide and natural renin substrate on vascular tone and to adrenergic stimuli. Alterations in the latter caused by angiotensinogen will be related to release, synthesis, storage and inactivation of norepinephrine. To distinguish the direct effects of angiotensin precursors on adrenergic transmission from those related to the enzymic generation of angiotensins, the actions of the former will be subsequently examined in the presence of inhibitors of the renin-angiotensin system. In vivo experiments will be performed on mesenteric vasculature of normal and nephrectomized animals to assess the role of extra-renal renin in the facilitation of adrenergic nervous activity. 2) Interactions of prostaglandins (PGs) and adrenergic nervous system. We will study the effect of PGs, PG precursors, PG synthetase inhibitors and cyclic endoperoxides on the release, synthesis, storage and inactivation of norepinephrine. Additional experiments will be performed in intact animals to define species and organ dependent actions of PGs on the vascular responses to adrenergic stimuli. 3) Interactions of kinins and adrenergic nervous system. The effect of kinins on vascular tone and adrenergic transmission will be examined. Similar experiments will be performed using kinins precursor (kininogen) in the presence and absence of kallikrein inhibitor (Trasylol) to define the possible role of endogenously generated kinins in the modulation of adrenergic transmission. We will also examine the effect of exogenous and locally generated angiotensins and kinins on the output of PGs and the consequence of this action on adrenergic transmission. We expect, thereby, to define the neural and hormonal elements of a system which may play an important role in the regulation of vascular tone and blood pressure.